Neoadjuvant Afatinib Window Study in Squamous Cell Carcinoma of the Head and Neck
The general objectives are to evaluate the pre-operative activity and the safety of afatinib in head and neck cancer and to explore the different downstream molecular pathways to identify tumor response and resistance mechanisms. The results from this study can be used to conduct a larger trial that would allow us to confirm or validate the hypotheses generated.
Carcinoma, Squamous Cell of Head and Neck
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Neoadjuvant Afatinib Based Treatment Strategies Followed by Surgery in Squamous Cell Carcinoma of the Head and Neck: an EORTC NOCI-HNCG Window Study.|
- Reduction of tumor Standardised Uptake Volume as assessed by FDGPET [ Time Frame: Baseline and after two weeks of treatment ] [ Designated as safety issue: No ]Afatinib will be given orally for 2 weeks from the day of randomization until day -1 prior to surgery at a dose of 40 mg/day.Pre-treatment biopsies and blood samples will be harvested during the regular diagnosis staging procedure and at surgery.FDG-PET/CT-scan and MRIs will be performed before treatment (before day -15) and the day before surgery.The primary outcome measure is the reduction in the tumor standardised uptake volume as assessed by FDGPET
- Evaluation of tumour response to treatment by different imaging modalities like DWIMRI and DCEMRI [ Time Frame: Baseline and after two weeks of treatment ] [ Designated as safety issue: No ]
Response after 2 weeks of treatment, prior to surgery, evaluated by:
- RECIST v1.1 using conventional imaging
- Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE MRI)
- Diffusion Weighted Imaging Magnetic Resonance Imaging (DWI MRI)
|Study Start Date:||July 2012|
|Estimated Study Completion Date:||March 2015|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Afatinib given orally for 2 weeks after randomization till day -1 prior to surgery (day 0) at a dose of 40 mg/day
Afatinib for 2 weeks at a dose of 40 mg/day
No treatment only observation
This is a randomized, multicenter early phase II trial exploring the pre-operative activity of afatinib vs. nontreatment. The study includes an early monitoring of the surgical co-morbidities for patients treated with afatinib and accrual may be stopped prematurely according to a pre-defined safety stopping rule.
Patients will be randomized with a 5:1 ratio, between the two arms: afatinib and 'no treatment'. It is intended to include a total of 30 eligible patients out of which 25 patients will be randomized into the afatinib arm.
Patients allocated to the 'no treatment' arm will mainly serve as a reference to interpret the results of the translational research part of the study although no formal comparison between the afatinib arm and the 'no treatment' arm is intended.
Patients will be first registered into the EORTC system after signing the informed consent form. The site will have to complete all the study related procedures within 4 weeks prior randomization and all eligibility criteria should be met before the patient can be randomized into the study.
The registration of patients will proceed with slots for patients which will be opened or closed based on the randomization of patients into the afatinib arm. Starting with 3 free slots, an additional slot will become available for each patient randomized to the 'no treatment' arm.
Registration will be paused after three completes the 4 week observation period after surgery. Similar action will be done after the next 3 patients have been entered into the afatinib arm.
Once the first 6 patients in the afatinib arm have been observed for surgical toxicities of grade ≥ 3 for 4 weeks following surgery, the slot system will cease to operate.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01538381
|Contact: Leslie V Herman, PhDfirstname.lastname@example.org|
|Cliniques Universitaires St. Luc||Recruiting|
|Brussels, Belgium, 1200|
|Institut Jules Bordet||Recruiting|
|Brussels, Belgium, 1000|
|U.Z. Leuven - Campus Gasthuisberg||Not yet recruiting|
|Leuven, Belgium, 3000|
|Istituto Nazionale Per Lo Studio E La Cura Dei Tumori||Recruiting|
|Milano, Italy, 20133|
|Study Chair:||Jean-Pascal Machiels, MD||European Organisation for Research and Treatment of Cancer - EORTC|
|Principal Investigator:||Lisa Licitra, MD||European Organisation for Research and Treatment of Cancer - EORTC|
|Principal Investigator:||Yassine Lalami, MD||European Organisation for Research and Treatment of Cancer - EORTC|
|Principal Investigator:||Paul Clement, MD||European Organisation for Research and Treatment of Cancer - EORTC|